Nayfeh, Tarek

Background: The global obesity epidemic has been well characterized over decades of research, linking increased body mass index (BMI) ≥ 25 to multiple medical conditions including increased cancer risk, morbidity, and mortality. The International Agency for Research on Cancer (IARC) group found a positive correlation between obesity to 13 cancers and multiple studies suggest leukemia should be added to this list. The causation behind this risk in leukemia however is not well understood and the prognostic factors have not been well characterized. Acute Myeloid Leukemia (AML) specifically defines risk based on cytogenetics between favorable, intermediate and unfavorable which significantly affects treatment decisions. The link between obesity and cytogenic risk factors in AML have not previously been thoroughly evaluated. To address this knowledge gap, we conducted a comprehensive meta-analysis aiming to evaluate the cytogenetic risk with obesity and prognostic significance in patients with AML. Methods: A systematic search was conducted across major databases until June 2023, using tailored search structures, subject headings, and keywords developed in collaboration with a medical research librarian. Two investigators independently screened the studies for inclusion. The inclusion criteria encompassed retrospective and prospective clinical studies that reported on the association between established cytogenetic classifications and standardized measures of excessive weight (BMI 25-30) and obesity (BMI ≥ 30). Meta-analysis was conducted using restricted maximum likelihood random-effects model. Results: From an initial pool of 1673 identified studies, eleven studies met the inclusion criteria, encompassing a total of 5887 patients. Among these patients, 1363 met the criteria for obesity (BMI ≥ 30) and 2176 met the criteria for excessive weight (BMI 25-30). The median patient's age was 54 (ranging from 15 to 89). The included studies originated from diverse geographic regions, including the USA, Japan, and France. Baseline patient characteristics are summarized in Table 1. Compared to overweight patients, our meta-analysis revealed a significant association between obesity and higher odds of unfavorable/intermediate cytogenetic risk (odds ratio [OR] 1.27, 95% CI [1.04; 1.54]), as seen in Figure 1. However, no meaningful statistical inference could be made regarding the association between obesity and specific gene mutations (such as FLT3, NPM1, CEBPa, TET2, IDH1, IDH2, RUNX1, and KRAS) due to the limited number of studies and small number of patients involved. Conclusion: Our meta-analysis demonstrates a significant association between obesity and unfavorable/ intermediate cytogenetic risk in patients with AML. Although the precise biological mechanisms remain elusive, several potential explanations have been proposed. These include the impact of obesity leading to chronic low-grade inflammation, altered adipokine secretion and insulin resistance, and metabolic changes on leukemic cell growth and survival. Despite the limitations of unknown cytogenetic risk in 590 patients and limited mutation data in some studies, our findings suggest that obesity may impact the prognosis of AML. Future research should address these limitations and provide a more comprehensive understanding of the intricate interplay between obesity, cytogenetics, and AML prognosis.

INTRODUCTION: Whether dye spray chromoendoscopy (DCE) adds value in surveillance colonoscopy with high-definition (HD) scopes remains controversial. This updated meta-analysis compares dysplasia detection using DCE and high-definition white light endoscopy (HD-WLE) in patients with inflammatory bowel disease (IBD) undergoing surveillance colonoscopy. METHODS: A comprehensive search was performed for randomized controlled trials (RCT) comparing HD-WLE and DCE in patients with IBD. The primary outcome was to compare the proportion of patients with at least 1 dysplastic lesion detected by DCE vs HD-WLE. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using the random-effects model, with I 2 > 60% indicating substantial heterogeneity. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence (CoE). RESULTS: Six RCT involving 978 patients were analyzed (DCE = 479 vs HD-WLE = 499 patients). DCE detected significantly more patients with dysplasia than HD-WLE (18.8% vs 9.4%), OR 1.94 (95% CI 1.21–3.11, I 2 = 28%, P = 0.006, high CoE). This remained significant after excluding 2 RCT published as abstracts. A sensitivity analysis excluding a noninferiority RCT with a single experienced operator eliminated the results' heterogeneity, OR 2.46 (95% CI 1.56–3.90, I 2 = 0%). Although high-grade dysplasia detection was numerically higher in the DCE group (2.8% vs 1.1%), the difference was statistically insignificant, OR 2.21 (95% CI 0.64–7.62, I 2 = 0%, low CoE). DISCUSSION: Our updated meta-analysis supports DCE as a superior strategy in overall dysplasia detection in IBD, even with HD scopes. When expertise is available, DCE should be considered for surveillance colonoscopy in patients with high-risk IBD, with the acknowledgment that virtual chromoendoscopy shows equivalence in recent studies. Further multicenter trials with multiple endoscopists with varying expertise levels and longer-term outcome data showing a reduction in cancer or cancer-related death are needed.

SummaryBackgroundProgression to cirrhosis in non‐alcoholic steatohepatitis (NASH) is associated with a decrease in liver fat. However, the prognostic significance of liver fat content in NASH‐related significant fibrosis and cirrhosis is unclear.AimTo investigate the risk of decompensation, hepatocellular carcinoma (HCC) and mortality stratified by liver fat content in NASH‐related significant fibrosis and cirrhosis.MethodsIn this meta‐analysis of individual participant data, 456 patients with both magnetic resonance elastography (MRE) and MRI‐derived protein density fat fraction (MRI‐PDFF) were enrolled, and 296 patients with longitudinal follow‐up were analysed. MRE combined with fibrosis‐4 (MEFIB‐index), and MRI‐PDFF were used to measure liver fibrosis and fat, respectively. MEFIB‐negative, MEFIB‐positive+ MRI‐PDFF ≥5% and MEFIB‐positive+ MRI‐PDFF <5% were defined as no significant liver fibrosis, NASH with significant fibrosis and higher liver fat content, and NASH with significant fibrosis and low liver fat content groups, respectively. The primary outcome was hepatic decompensation, HCC and death.ResultsThe rates of decompensation, HCC and mortality were highest in the NASH with significant fibrosis and low liver fat group (33%, 17% and 17%, respectively), followed by the NASH with significant fibrosis and higher liver fat group (18%, 13% and 13% respectively), and lowest in the no significant fibrosis (MEFIB‐negative) group (0%, 1% and 2% respectively). In multivariable‐adjusted analysis, low liver fat content was strongly associated (HR = 42.2 [95% CI: 7.5–235.5, p < 0.0001]) with HCC, decompensation and death. Sensitivity analyses for patients with cirrhosis (MRE ≥5 kPa) determined consistent findings.ConclusionsLow liver fat content in patients with burnt‐out NASH‐related significant fibrosis and cirrhosis is associated with an increase in hepatic decompensation, HCC and mortality.

Summary Background There are limited data regarding the longitudinal association between MEFIB‐Index (MRE combined with FIB‐4) versus MAST‐Score (MRI‐aspartate aminotransferase) and hepatic decompensation. Aim To examine the longitudinal association between MEFIB‐Index versus MAST‐Score in predicting hepatic decompensation in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD). Methods This was a longitudinal, retrospective analysis of subjects from United States, Japan, and Turkey who underwent a baseline MRE and MRI‐PDFF and were followed for hepatic decompensation. Cox‐proportional hazard analyses were used to assess the association between MEFIB‐Index versus MAST‐Score with a composite primary outcome (hepatic decompensation) defined as ascites, hepatic encephalopathy, and varices needing treatment. Results This meta‐analysis of individual participants (IPDMA) included 454 patients (58% women) with a mean (±SD) age of 56.0 (±13.5) years. The MEFIB‐Index (MRE ≥3.3 kPa + FIB 4 ≥1.6) and MAST‐Score (>0.242) were positive for 34% and 9% of the sample, respectively. At baseline, 23 patients met criteria for hepatic decompensation. Among 297 patients with available longitudinal data with a median (IQR) of 4.2 (5.0) years of follow‐up, 25 incident cases met criteria for hepatic decompensation. A positive MEFIB‐Index [HR = 49.22 (95% CI: 6.23–388.64, p < 0.001)] and a positive MAST‐Score [HR = 3.86 (95% CI: 1.46–10.17, p < 0.001)] were statistically significant predictors of the incident hepatic decompensation. MEFIB‐Index ( c ‐statistic: 0.89, standard error (SE) = 0.02) was statistically superior to the MAST‐Score ( c ‐statistic: 0.81, SE = 0.03) ( p < 0.0001) in predicting hepatic decompensation. Conclusion A combination of MRI‐based biomarker and blood tests, MEFIB‐Index and MAST‐Score can predict the risk of hepatic decompensation in patients with MASLD.

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06–1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12–1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22–1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10–1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.

Introduction: Patients with acute heart failure (AHF) exacerbation are susceptible to complications in the setting of COVID-19 infection. Data regarding the clinical outcomes of COVID-19 in patients admitted with AHF is limited. Methods: We used the national inpatient sample database by utilizing ICD-10 codes to identify all hospitalizations with a diagnosis of AHF in 2020. We classified the sample into AHF with COVID-19 infection versus those without COVID-19. Primary outcome was in-hospital mortality. Secondary outcomes were acute myocardial infarction, need for pressors, mechanical cardiac support, cardiogenic shock, and cardiac arrest. Also, we evaluated for acute pulmonary embolism (PE), bacterial pneumonia, need for a ventilator, and acute kidney injury (AKI). Results: We identified a total of 694,920 of AHF hospitalizations, 660,463 (95.04%) patients without COVID-19 and 34,457 (4.96%) with COVID-19 infection. For baseline comorbidities, diabetes mellitus, chronic heart failure, ESRD, and coagulopathy were significantly higher among AHF patients with COVID-19 ( P < .01). While CAD, prior MI, percutaneous coronary intervention, and coronary artery bypass graft, atrial fibrillation, chronic obstructive pulmonary disease, and peripheral vascular disease were higher among those without COVID-19. After adjustment for baseline comorbidities, in-hospital mortality (aOR 5.08 [4.81 to 5.36]), septic shock (aOR 2.54 [2.40 to 2.70]), PE (aOR 1.75 [1.57 to 1.94]), and AKI (aOR 1.33 [1.30 to 1.37]) were significantly higher among AHF with COVID-19 patients. The mean length of stay (5 vs 7 days, P < .01) and costs of hospitalization ($42,143 vs $60,251, P < .01) were higher among AHF patients with COVID-19 infection. Conclusion: COVID-19 infection in patients with AHF is associated with significantly higher in-hospital mortality, need for mechanical ventilation, septic shock, and AKI along with higher resource utilization. Predictors for mortality in AHF patients during the COVID-19 pandemic, COVID-19 infection, patients with end-stage heart failure, and atrial fibrillation. Studies on the impact of vaccination against COVID-19 in AHF patients are needed

Abstract Background Early-stage breast cancer is among the most common cancer diagnoses. Adjuvant radiotherapy is an essential component of breast-conserving therapy, and several options exist for tailoring its extent and duration. This study assesses the comparative effectiveness of partial-breast irradiation (PBI) compared with whole-breast irradiation (WBI). Methods A systematic review was completed to identify relevant randomized clinical trials and comparative observational studies. Independent reviewers working in pairs selected studies and extracted data. Randomized trial results were pooled using a random effects model. Prespecified main outcomes were ipsilateral breast recurrence (IBR), cosmesis, and adverse events (AEs). Results Fourteen randomized clinical trials and 6 comparative observational studies with 17 234 patients evaluated the comparative effectiveness of PBI. PBI was not statistically significantly different from WBI for IBR at 5 years (RR = 1.34, 95% CI = 0.83 to 2.18; high strength of evidence [SOE]) and 10 years (RR = 1.29, 95% CI = 0.87 to 1.91; high SOE). Evidence for cosmetic outcomes was insufficient. Statistically significantly fewer acute AEs were reported with PBI compared with WBI, with no statistically significant difference in late AEs. Data from subgroups according to patient, tumor, and treatment characteristics were insufficient. Intraoperative radiotherapy was associated with higher IBR at 5, 10, and over than 10 years (high SOE) compared with WBI. Conclusions Ipsilateral breast recurrence was not statistically significantly different between PBI and WBI. Acute AEs were less frequent with PBI. This evidence supports the effectiveness of PBI among selected patients with early-stage, favorable-risk breast cancer who are similar to those represented in the included studies.

e19543 Background: Primary Bone Lymphoma (PBL) is defined as a lymphoma originating in an osseous site with no systemic disease. It is rare, constituting around 1% of all lymphomas. Due to its rarity, ascertaining natural history and standard of care treatments are based primarily on small case series but there have been no systematic reviews, randomized control trials or meta-analysis to establish optimal treatment strategies. Methods: We searched MEDLINE, Embase, Scopus and other sources, from each database's inception to September 2022. Outcomes of interest included mortality and progression at different time points, as well as complete response and partial response. Meta-analysis was conducted using the random-effects model. Results: The number of studies matching our inquiry was 51 ranging from 1955 to 2019. Total patients studied were 5,847 of which 3,055 were male and the dominant histology was diffuse large B cell lymphoma with 3,816. Treatment primarily consisted of radiation therapy, chemotherapy, or a combination of the two. Overall mortality at 2, 5 and 10 years was 17%, 29% and 39% respectively. Complete response to initial treatment was noted in 73% of patients. Disease progression at 2 and 5 years was 26% and 29% respectively. Patients aged older than 60 years and multiple sites of disease in the skeleton (such as axial and spine etc.) had worse outcomes with RR 1.76 (P value 0.0027) and 1.133 (P value 0.0167) respectively. Additionally, patients who underwent chemotherapy with radiation vs radiation alone had improved outcomes with a relative risk of 0.38 (P value of 0.0001). Patients who underwent radiation treatment in addition to chemotherapy tended to have improved outcomes with a relative risk of 0.60 but this was not statistically significant with a P value of 0.068. Conclusions: We performed a systematic review to determine the characteristics and current treatment of PBL. The analysis demonstrates the rarity and heterogenicity of the disease. The current standard of care is for chemoradiation, but this is based primarily on old case studies. Our study confirms the utility of multimodal treatment with a tendency for improved outcomes. However, further prospective trials are needed to determine the necessity of multimodal treatment given this hypothesis generating study. [Table: see text]

Liver transplant (LT) has become increasingly common among reproductive-aged women. The effect of the type of liver donor, either a living donor LT (LDLT) or a deceased donor LT, on pregnancy outcomes is unknown. As such, we aim to review the available literature and assess obstetric, pregnancy, or delivery outcomes in LDLT. We conducted a comprehensive literature review of MEDLINE, EMBASE, Cochrane, and Scopus databases. Random-effect meta-regression assessed the association between the percentage of women who underwent LDLT (independent variable) and the proportion of outcomes. Meta-regression results were expressed as a regression coefficient, which transforms the proportion of outcomes of interest associated with a 1% increase in the percentage of LDLT patients. A value of 0 denotes no relationship between the outcomes and LDLT. A total of 6 articles (438 patients) were included, with a total of 806 pregnancies. Eighty-eight (20.09%) patients underwent LDLT. None of the studies segregated the data based on the type of donor LT. The median time from LT to pregnancy was 4.86 (4.62–5.03) years. Twelve (1.5%) stillbirths were reported. LDLT was statistically significantly associated with a higher rate of stillbirths (coefficient 0.002, p < 0.001; I2 0%). The type of donor LT was not associated with an increased risk of other obstetric, pregnancy, or delivery complications. This is the first meta-analysis to evaluate the effect of the type of donor LT on pregnancy outcomes. This study highlights the lack of robust literature addressing this important topic. The results suggest that pregnancy outcomes after LDLT and deceased donor LT are comparable. Despite LDLT being statistically significantly associated with a higher rate of stillbirths, the association is weak and is unlikely to be clinically significant.

Abstract Background Peripherally inserted central catheters (PICCs) and midlines are commonly used devices for reliable vascular access. Infection and thrombosis are the main adverse effects of these catheters. We aimed to evaluate the relative risk of complications from midlines and PICCs. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. The primary outcomes were catheter-related bloodstream infection (CRBSI) and thrombosis. Secondary outcomes evaluated included mortality, failure to complete therapy, catheter occlusion, phlebitis, and catheter fracture. The certainty of evidence was assessed using the GRADE approach. Results Of 8368 citations identified, 20 studies met the eligibility criteria, including 1 RCT and 19 observational studies. Midline use was associated with fewer patients with CRBSI compared with PICCs (odds ratio [OR], 0.24; 95% CI, 0.15–0.38). This association was not observed when we evaluated risk per catheter. No significant association was found between catheters when evaluating risk of localized thrombosis and pulmonary embolism. A subgroup analysis based on location of thrombosis showed higher rates of superficial venous thrombosis in patients using midlines (OR, 2.30; 95% CI, 1.48–3.57). We did not identify any significant difference between midlines and PICCs for the secondary outcomes. Conclusions Our findings suggest that patients who use midlines might experience fewer CRBSIs than those who use PICCs. However, the use of midline catheters was associated with greater risk of superficial vein thrombosis. These findings can help guide future cost-benefit analyses and direct comparative RCTs to further characterize the efficacy and risks of PICCs vs midline catheters.